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ABBREVIATED PRESCRIBING INFORMATION

ONTOZRY▼(cenobamate) 12.5mg, 25mg, 50mg, 100mg, 150mg and 200mg tablets

Please refer to the full Summary of Product Characteristics (SmPC) before prescribing, particularly in relation to adverse reactions, precautions and contraindications.

Presentations: Tablets containing 12.5 mg 25mg, 50 mg, 100mg, 150mg, 200 mg of cenobamate.

Indication (GB): Ontozry is indicated for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in adult patients with epilepsy who have not been adequately controlled despite treatment with at least 2 anti-epileptic medicinal products.

Indication (NI): Ontozry is indicated for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in adult patients with epilepsy who have not been adequately controlled despite a history of treatment with at least 2 anti-epileptic medicinal products.

Dosage and administration: for oral once daily administration. The tablets cannot be split accurately as there is no break line and the accuracy of the dose cannot be ensured. Adults: recommended starting dose of cenobamate is 12.5 mg per day, titrated gradually to the recommended target dose of 200 mg per day. Based on clinical response, dose may be increased to a maximum of 400 mg per day. Please refer to the full Summary of Products Characteristics for further information on the recommended titration schedule, which should not be exceeded because of the potential for serious adverse reactions, Elderly (≥65 years): Clinical studies of cenobamate did not include sufficient numbers of subjects aged 65 and over, to determine whether they responded differently from younger patients.
Paediatric population: No data are available.
Hepatic or renal impairment: Caution should be used for patients with renal or hepatic impairment. Cenobamate should not be used in patients with end-stage renal disease or patients undergoing haemodialysis. Cenobamate should not be used in patients with severe hepatic impairment.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Familial Short-QT syndrome.

Special warnings and precautions: Patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, has been reported in association with cenobamate when started at higher doses and titrated rapidly (weekly or faster titration). When cenobamate was initiated at 12.5 mg/day and titrated every two weeks, no cases of DRESS were reported. Patients should be advised of the signs and symptoms of DRESS and monitored closely for skin reactions. Symptoms of DRESS include typically, although not exclusively, fever, rash associated with other organ system involvement, lymphadenopathy, liver function tests abnormalities and eosinophilia. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If signs and symptoms suggestive of these reactions appear, cenobamate should be withdrawn immediately and an alternative treatment considered (as appropriate). QT-shortening - a dose-dependent shortening of the QTcF interval has been observed with cenobamate. Reductions of the QTcF interval below 340 msec were not observed. In clinical trials there was no evidence that the combination of cenobamate with other antiepileptic medicines led to further QT-shortening. Clinicians should use caution when prescribing cenobamate in combination with other medicinal products that are known to shorten the QT.
This drug contains lactose and patients with rare hereditary problems such as galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Interaction with other medicinal products and other forms of interaction: Cenobamate may reduce exposures of products primarily metabolized by CYP3A4 and 2B6. Cenobamate may increase exposures of products primarily metabolized by CYP2C19. When initiating or discontinuing treatment with cenobamate or changing the dose, it may take 2 weeks to reach the new level of enzyme activity. Pharmacodynamic Interactions: CNS depressants: concomitant use of cenobamate with other CNS depressants, including alcohol, barbiturates, and benzodiazepines may increase the risk of neurological adverse reactions and relevant doses may need to be reduced. Interactions with other antiepileptics: Phenytoin, Phenobarbital - no dose adjustment of cenobamate is required. Phenytoin and phenobarbital concentrations should be monitored during titration of cenobamate, and based on individual response, the dose of phenytoin and phenobarbital may need to be reduced. Clobazam: no dose adjustment of cenobamate is required. Due to a possible increase in exposure of the active metabolite of clobazam (N-desmethylclobazam), the dose of clobazam may need to be reduced. Lamotrigine - depending on individual response, the dose of cenobamate may need to be increased. Carbamazepine, Valproic Acid, Lacosamide, Leviracetam and Oxcarbazepine - no dose adjustments are required. Other medicinal products. Oral contraceptives - women of reproductive potential concomitantly using oral contraceptives should practice additional or alternative non-hormonal measures of birth control. CYP3A4 substrates - an increase in the dose of medicines metabolized by CYP3A4 may be required when used concomitantly with cenobamate. CYP2B6 substrates - an increase in the dose of medicines metabolized by CYP2B6 may be required when used concomitantly with cenobamate. CYP2C19 substrates - a dose reduction of medicines metabolized by CYP2C19 may be required when used concomitantly with cenobamate. OAT3 substrates - concomitant administration of cenobamate and medicinal products transported by OAT3 (e.g. baricitinib, cefaclor, empagliflozin, penicillin G, ritobegron, and sitagliptin) may result in higher exposure of these medicinal products. Please refer to SmPC for all information on drug interactions

Fertility, pregnancy, lactation - Fertility: The effects of cenobamate on human fertility are unknown. Animal data are insufficient due to exposure below clinical levels. Pregnancy: there are no adequate data from the use of cenobamate in pregnant women. Animal studies have shown that cenobamate crosses the placenta. Studies in animals have shown reproductive toxicity at levels below clinical exposure. Cenobamate should not be used during pregnancy unless the clinical condition of the woman requires treatment with cenobamate. Cenobamate is not recommended in women of childbearing potential not using contraception. Women of reproductive potential concomitantly using oral contraceptives should practice additional or alternative non-hormonal measures of birth control during treatment with cenobamate and until 4 weeks after treatment discontinuation. Lactation: As a precautionary measure, breast-feeding should be discontinued during treatment with cenobamate

Effects on ability to drive and use machines- Cenobamate may cause somnolence, dizziness, fatigue, impaired vision and other CNS-related symptoms, which may influence the ability to drive or use machines. Patients are advised not to drive a vehicle, operate complex machinery or engage in other potentially hazardous activities until it is known whether cenobamate affects their ability to perform these tasks.

Undesirable effects - the most commonly reported adverse reactions were Somnolence, Coordination and Gait abnormalities, and Headaches. The adverse reactions most commonly leading to discontinuation, in descending order of frequency, were ataxia (1.6% vs 0.5% placebo), dizziness (1.6% vs 0.5% placebo), somnolence (1.4% vs 0.5% placebo), nystagmus (0.7% vs 0% placebo), vertigo (0.7% vs 0% placebo), and diplopia (0.5% vs 0% placebo). Adverse reactions reported in clinical trials: Very common: Somnolence, Coordination and Gait abnormalities, Headache. Common: confusional state, irritability, dysarthria, nystagmus, aphasia, memory impairment, diplopia, vision blurred, constipation, diarrhoea, nausea, vomiting, dry mouth, rash, hepatic enzyme increased. Hypersensitivity: four patients (0.9%) experienced an event of hypersensitivity, including one patient who experienced eyelid oedema. All events were classified as mild or moderate. Drug reaction with eosinophilia and systemic symptoms (DRESS) - three cases of DRESS were reported within 2 to 4 weeks of starting cenobamate in studies with high starting doses (50 mg or 100 mg once daily) and weekly or faster titration. At the time of prescription, patients should be advised of the signs and symptoms of DRESS and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, cenobamate should be withdrawn immediately and an alternative treatment considered (as appropriate). Prescribers should consult the SmPC in relation to all adverse events. Reporting suspected adverse reactions after authorisation of the medicinal product is important. Healthcare professionals are asked to report any suspected adverse reactions via the National reporting system.

Legal Classification - Prescription only medicine (POM).
Package Quantity and Price -
Ontozry 12.5mg tablets x14, Ontozry 25mg film-coated tablets x 14 (total 28) £165.62
Ontozry 50mg film-coated tablets x 14 £85.54
Ontozry 100mg film-coated tablets x 14 £87.36
Ontozry 150mg film-coated tablets x 14 £89.18
Ontozry 200mg film-coated tablets x 14 £91.00
Ontozry 50mg film-coated tablets x 28 £91.00
Ontozry 100mg film-coated tablets x 28 £136.50
Ontozry 150mg film-coated tablets x 28 £182.00
Ontozry 200mg film-coated tablets x 28 £182.00

Marketing Authorization Holder (GB) - Arvelle Therapeutics Netherlands B.V. Zuidplein 36
1077 XV Amsterdam - The Netherlands
Marketing Authorization Holder (NI) - Angelini Pharma S.p.A, Viale Amelia 70, 00181, Rome –Italy

Marketing Authorisation numbers (GB) - PLGB 53287/0001-0007
Marketing Authorisation numbers (NI) - EU/1/21/1530/001

Date of preparation - November 2021

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should be reported to Arvelle Therapeutics UK on 02034889643 or UKIReporting@angelinipharma.com

P-UK-CE-2100025 | December 2021

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